P-36 Real-world outcomes in BRAFV600E metastatic colorectal cancer – the Glasgow experience
Authors: H. Gan, M. White, G. McGaffin, T. Lannagan, A. Campbell, J. Graham, O. Sansom, R. Wilson
Journal: Annals of Oncology (2022)

Approximately 8 - 10% of metastatic colorectal cancers (mCRC) have a BRAF V600E mutation. BRAF V600E mutant mCRC represents a distinct clinical subset with a poor prognosis. Previous treatment guidelines have been derived from subgroup analyses of non-designated BRAF V600E trials. Real world studies have shown that outcomes and treatment practices can vary widely. Here, we report on our regional practices and outcomes. We undertook a retrospective analysis of all mCRC patients with confirmed BRAF V600E mCRC diagnosed in NHS Greater Glasgow and Clyde Health Board (Scotland, UK) between 01/01/2015 - 31/12/2020. Clinical and pathological features were obtained from electronic records. Univariate analysis of prognostic factors was performed using Kaplan Meier analysis and log-rank test. Multivariate analysis was performed using Cox regression. A total of 139 patients were identified for study with 1 excluded for missing follow up information. Median age at metastatic diagnosis was 69 years, with a female preponderance (59% female, 41% male). 31% of tumours also had deficient mismatch repair (dMMR) or high levels of microsatellite instability (MSI-H). Primary tumour site was mostly right-sided (n=102, 74%), with less left-sided (n=20, 15%) and rectal (n=15, 11%) tumours. 1 patient had 2 synchronous primaries (1 right colon and 1 rectal). 64% presented with de novo metastatic disease. For those with initial loco-regional disease, the median time to metastatic progression was 10 months. The most common metastatic sites were liver (54%), peritoneal (33%), lymph node (31%), and lung (28%). 36% of patients did not receive any systemic treatment, 36% received 1 line, and 28% received 2 or more lines of treatment. Most (69%) received a cytotoxic chemotherapy doublet as first-line treatment, and 6% received triplet cytotoxic chemotherapy. 7% received immunotherapy. Among the treated patients, only 19% received some form of targeted therapy over their full treatment course, usually a combination containing an anti-EGFR inhibitor. The median overall survival was poor at 7.2 months. Features significantly associated with shorter survival were performance status (PS) of 2 or worse (p < 0.01), the presence of lymph node metastasis (p = 0.010) and peritoneal metastasis (p < 0.01), a higher modified Glasgow Prognostic Score (GPS) of 2 (p = 0.035) and a high neutrophil-lymphocyte ratio >5 (p = 0.032). Primary tumour site was also significantly associated with survival (p < 0.01), with worse survival for right-sided tumours (6.6 months), compared to 14.0 months for left-sided/rectal tumours. Using multivariate analysis, independent prognostic markers were PS, presence of lymph node metastasis, presence of peritoneal metastasis and right-sided primary tumour location. This is a representative cohort of BRAF V600E metastatic colorectal cancer patients, which confirms previously known clinical features. Of the common metastatic sites, peritoneal or lymph node metastases confer a poorer prognosis. There was not widespread adoption of more intensive triplet chemotherapy over the study time period. Overall survival is poor, and changed treatment strategies facilitated by recent clinical trial advances with targeted therapies may improve outcomes in this poor prognostic group.